Synergistic Toll-like Receptor 3/9 Signaling Affects Properties and Impairs Glioma-Promoting Activity of Microglia

被引：30

作者：

Huang, Yimin ^{[1
,2
]}

Zhang, Quan ^{[3
]}

Lubas, Malgorzata ^{[1
]}

Yuan, Yang ^{[1
]}

Yalcin, Fatih ^{[1
,4
]}

Efe, Ibrahim E. ^{[1
]}

Xia, Pengfei ^{[1
]}

Motta, Edyta ^{[1
]}

Buonfiglioli, Alice ^{[1
,5
]}

Lehnardt, Seija ^{[5
]}

Dzaye, Omar ^{[6
,7
,8
,9
,10
]}

Flueh, Charlotte ^{[1
,4
]}

Synowitz, Michael ^{[4
]}

Hu, Feng ^{[3
]}

Kettenmann, Helmut ^{[1
]}

机构：

[1] Helmholtz Assoc, Max Delbruck Ctr Mol Med, Cellular Neurosci, D-13125 Berlin, Germany

[2] Charite, D-10117 Berlin, Germany

[3] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Neurosurg, Wuhan 430030, Hubei, Peoples R China

[4] Univ Med Ctr Schleswig Holstein, Dept Neurosurg, D-24105 Kiel, Germany

[5] Charite, Inst Cell Biol & Neurobiol, Dept Neurol, D-10117 Berlin, Germany

[6] Johns Hopkins Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA

[7] Charite Univ Med Berlin, Dept Radiol, D-13353 Berlin, Germany

[8] Free Univ Berlin, D-13353 Berlin, Germany

[9] Humboldt Univ, D-13353 Berlin, Germany

[10] Berlin Inst Hlth, D-13353 Berlin, Germany

来源：

JOURNAL OF NEUROSCIENCE | 2020年 / 40卷 / 33期

基金：

中国国家自然科学基金;

关键词：

brain macrophage; costimulation; glioma; microglia; Toll-like receptor 3; Toll-like receptor 9; CPG OLIGONUCLEOTIDE; MT1-MMP EXPRESSION; PHASE-II; CANCER; MACROPHAGES; CELLS; IMMUNOTHERAPY; GLIOBLASTOMA; BETA; OPPORTUNITIES;

D O I：

10.1523/JNEUROSCI.0666-20.2020

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

In murine experimental glioma models, TLR3 or TLR9 activation of microglial/macrophages has been shown to impair glioma growth, which could, however, not been verified in recent clinical trials. We therefore tested whether combined TLR3 and TLR9 acti-vation of microglia/macrophages would have a synergistic effect. Indeed, combined TLR3/TLR9 activation augmented the suppression of glioma growth in organotypic brain slices from male mice in a microglia-dependent fashion, and this synergistic suppression depended on interferon b release and phagocytic tumor clearance. Combined TLR3/TLR9 stimulation also augmented several func-tional features of microglia, such as the release of proinflammatory factors, motility, and phagocytosis activity. TLR3/TLR9 stimulation combined with CD47 blockade further augmented glioma clearance. Finally, we confirmed that the coactivation of TLR3/TLR9 also augments the impairment of glioma growth in vivo. Our results show that combined activation of TLR3/TLR9 in microglia/macro-phages results in a more efficient glioma suppression, which may provide a potential strategy for glioma treatment.

引用

页码：6428 / 6443

页数：16

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